Design, synthesis and anticancer activity of piperazine hydroxamates and their histone deacetylase (HDAC) inhibitory activity

被引：50

作者：

Chetan, Bhadaliya ^{[1
]}

Bunha, Mahesh ^{[1
]}

Jagrat, Monika ^{[1
]}

Sinha, Barij Nayan ^{[1
]}

Saiko, Philipp ^{[1
]}

Graser, Geraldine ^{[2
]}

Szekeres, Thomas ^{[2
]}

Raman, Ganapathy ^{[3
]}

Rajendran, Praveen ^{[3
]}

Moorthy, Dhatchana ^{[3
]}

Basu, Arijit ^{[1
]}

Jayaprakash, Venkatesan ^{[1
]}

机构：

[1] Birla Inst Technol, Dept Pharmaceut Sci, Ranchi 835215, Jharkhand, India

[2] Gen Hosp Vienna Med Univ Vienna, Dept Med & Chem Lab Diagnost, A-1090 Vienna, Austria

[3] Orchid Res Labs Ltd, Madras 600119, Tamil Nadu, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 13期

关键词：

Histone deacetylase inhibitors; Piperazine linker; Hydroxamates; RR pharmacophore; ASSAY; AGENTS; PROLIFERATION;

D O I：

10.1016/j.bmcl.2010.05.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Six compounds were synthesized with piperazine in linker region and hydroxamate as Zinc Binding Group ( ZBG). They were screened against three cancer cell-lines (NCIH460; HCT116; U251). Compounds 5c and 5f with GI(50) value of 9.33 +/- 1.3 mu M and 12.03 +/- 4 mu M, respectively, were tested for their inhibitory potential on hHDAC8. Compound 5c had IC(50) of 33.67 mu M. Compounds were also screened for their anticancer activity against HL60 human promyelocytic leukemia cell line due to the presence of pharmacophoric features of RR inhibitors in them. Compound 5c had IC(50) of 0.6 mu M at 48 h. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3906 / 3910

页数：5

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